It is proposed to investigate the biosynthesis of three novel microbial metabolites. These are the azoxy compound elaiomycin, which is produced by Streptomyces gelaticus, the hepatotoxic peptide cyclochloratine, which is produced by Penicillium islandicum, and the antitumor agent sparsomycin, which is found in cultures of Streptomyces sparsogenes. Earlier work has established the primary building blocks for elaiomycin and the focus of current efforts will be upon the mechanism of formation of the azoxy linkage. Cyclochloratine contains two unusual amino acid residues whose biosynthesis will be investigated: a cis 3,4-dichloroproline residue and a Beta-phenylalanine residue. The possible formation of these unusual amino acids from proline and phenylalanine will be evaluated. Sparsomycin contains a highly modified uracil moiety linked to a three carbon unit bearing a mono-oxo-dithioacetal group. Two hypotheses for the origin of the uracil moiety will be investigated and the hypothesis that the three carbon unit is derived from cysteine will be tested. The biosynthesis of the mono-oxo-dithioacetal group will also be scrutinized. The method utilized in these studies will be the administration of specifically labeled precursors to the appropriate organisms followed by location of the labels in the natural products by degradation or c.m.r. spectrometry.
|Parry, R J; Yang, N (1992) Isolation and characterization of furanomycin nonproducing Streptomyces threomyceticus mutants. J Antibiot (Tokyo) 45:1161-6|